Journal Article

Femethane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2

Terentieva, Ekatherine I, Khotskin, Nikita V, Antonova, Sophia M, Komleva, Polina D, Moskaliuk, Vitalii S, Kulikov, Alexander V, Shamshurin, Maxim V, Sokolov, Maxim N

2026

Overview

Pharmacological chaperones (PCs)—small molecules that normalize the 3D structure of mutant protein molecules—are promising substances for pharmacological treatment of grave hereditary pathologies. In this study, possible chaperone-like effects of the Fe(II) with tris(1-pyrasolyl)methane complex, [Fe(TPM)[sub.2]]Cl[sub.2], on the mutant 447R form of mouse tryptophan hydroxylase 2 (TPH2) in vitro and in vivo were investigated. The experiments were carried out on Balb/c mice homozygous for the mutant TPH2. This complex in concentrations of 0.01, 0.05 and 0.1 mM markedly increased the temperature (T[sub.50]) and free energy (ΔG) of the mutant TPH2 thermal denaturation in vitro. Seven intramuscular administrations of 30 and 60 mg/kg of [Fe(TPM)[sub.2]]Cl[sub.2] markedly increased the TPH2 activity in the midbrain of Balb/c mice. This increase in the TPH2 activity was not accompanied with an increase in the Tph2 gene mRNA and TPH2 protein levels. It is the first demonstration of chaperone-like activity of [Fe(TPM)[sub.2]]Cl[sub.2]. This complex is a promising chemical for correction of genetic alterations in TPH2 and the associated hereditary psychic disorders.

• Publisher: MDPI AG
• Subject: Animal experimentation / Denaturation / Hydroxylases / Medical research / Medicine, Experimental / Methane / Proteins / Sapropterin dihydrochloride / Tryptophan